Retinal Ganglion Cell Dysfunction in Asymptomatic G11778A: Leber Hereditary Optic Neuropathy

Guy, John; Feuer, William J.; Porciatti, Vittorio; Schiffman, Joyce C.; Abukhalil, Fawzi; Vandenbroucke, Ruth; Rosa, Potyra R.; Lam, Byron L.

doi:10.1167/iovs.13-13365

Cited by 49 publications

(35 citation statements)

References 37 publications

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“…Studies have examined the possible influence of an X-linked visual loss susceptibility locus, impaired mitochondrial respiratory chain activity, mtDNA heteroplasmy, environmental factors, and autoimmune factors [5,6]. e clinical characteristics of LHON are well documented [7][8][9][10], but fewer studies have compared visual electrophysiology with optical coherence tomography (OCT) of the retinal ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) in different stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and Structural Changes in Chinese Patients with LHON

Wang

Guo

et al. 2020

Journal of Ophthalmology

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Objective. To review retrospectively the electrophysiological and structural changes in 13 Chinese patients with Leber hereditary optic neuropathy (LHON). Methods. 26 eyes of 13 patients with a genetically confirmed diagnosis of LHON were categorized into two groups according to the duration of the disease: group 1 (duration less than 3 months) and group 2 (duration between 3 months and 18 years). Clinical history, comprehensive visual electrophysiology, optical coherence tomography (OCT), and color fundus photography were performed. Results. Fundoscopy showed optic disc hyperemia in group 1 and optic atrophy in group 2. OCT measures of retinal nerve fiber layer (RNFL) thickness around the optic disc and surrounding macula were normal in group 1 but reduced in group 2 (10 of 10 eyes). The thickness of the retinal ganglion cell layer (GCL) plus inner plexiform layer (IPL) surrounding the macula reduced significantly in group 1 and group 2 compared with a healthy control group. Pattern ERG (PERG) P50 amplitude was normal, but the N95/P50 ratio reduced in most of group 1 (4 of 5 eyes) and in all of group 2 (11 eyes). PERG P50 peak time was abnormally short in group 2. Multifocal electroretinography (mfERG) showed subnormal responses associated with ring 1 (the central area) and ring 2 in group 1 and reductions in rings 1, 2, and 3 in group 2. Conclusion. The study highlights differences in retinal structure and function between the acute and chronic stages of LHON in a group of Chinese patients. There is PERG evidence of retinal ganglion cell dysfunction and OCT evidence of GCL + IPL thinning in both groups, but there is additional peripapillary RNFL loss in the chronic stage, associated with more severe RGC dysfunction. There is multifocal ERG evidence of localized macular dysfunction in both acute and chronic groups. The study highlights the importance of comprehensive electrophysiological and structural assessments of the retina in LHON and is pertinent to studies that aim to monitor disease progression or the effects of future therapeutic interventions.

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Section: Introductionmentioning

confidence: 99%

Electrophysiological and Structural Changes in Chinese Patients with LHON

Wang

Guo

et al. 2020

Journal of Ophthalmology

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“…1,2 It has been reported that the axons in the papillomacular bundle are the most susceptible to injury in LHON due to preferential involvement of smaller axons. 3 Recent studies have detected subclinical ganglion cell dysfunction in asymptomatic carriers using pattern electroretinogram, and structural changes of the GCC on OCT. 4,5 High-definition optical coherence tomography (OCT) has shed some light on the events occurring at the optic nerve head in LHON, including a more clear depiction of axonal swelling, which occurs before and during the time of visual loss. Furthermore, OCT clearly detects atrophy of the nerve fibre layer (RNFL) following the acute event, which in most cases is confined to the maculopapillary bundle.…”

Section: Introductionmentioning

confidence: 99%

The Optical Coherence Tomographic Profile of Leber Hereditary Optic Neuropathy

Hedges

Gobuty

Manfready

et al. 2016

Neuro-Ophthalmology

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The objective of this study was to describe the changes in the retinal ganglion cell complex (GCC) relative to the retinal nerve fibre layer (RNFL) over time in Leber hereditary optic neuropathy (LHON) patients. Average RNFL and GCC thickness was measured in seven patients in the early acute (123, 68.4 μm), late acute (113.5, 57.4 μm), and chronic (72.7, 50.8 μm) phases. Patients showed thinning of the GCC with RNFL swelling in the early acute phase. GCC thinning became severe within weeks and persisted. RNFL swelling normalised during the late acute phase with eventual thinning in the chronic phase. GCC changes appear at the commencement of visual loss and in some cases prior to vision loss. These findings define an optical coherence tomography (OCT) profile in LHON.ARTICLE HISTORY

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“…Pattern electroretinographic responses originate in retinal ganglion cells. The loss and the progressive dysfunction in the macular ganglion cell layer might explain the reduced N95 component previously reported by Ziccardi et al and Guy et al in carriers . Thus the presence of macular ganglion cell layer focal thinning could be a sign that just reflects carrier status, not necessarily preceding disease development.…”

Section: Discussionmentioning

confidence: 78%

“…These abnormalities included peripapillary microangiopathy, localised swelling of the peripapillary retinal nerve fibre layer and visual fields defects . Similarly, abnormalities in colour vision and in pattern electroretinographic responses have also been described in asymptomatic carriers …”

Section: Discussionmentioning

confidence: 95%